Pharmacogenetics to prevent heparin-induced thrombocytopenia: what do we know?

• Published in: Pharmacogenomics Vol. 19; no. 18; pp. 1413 - 1422
• Main Author: Karnes, Jason H
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.12.2018
• Subjects: Alleles; anticoagulant; Anticoagulants; Anticoagulants - adverse effects; Antigens; biomarker; Biomarkers; Blood platelets; Consortia; Drug dosages; Fc receptors; Genetic Markers - genetics; genetics; genome-wide association study; Genotype & phenotype; Health risk assessment; Heparin; Heparin - adverse effects; heparin-induced thrombocytopenia; Histocompatibility antigen HLA; Humans; Immune response; Immunoglobulins; Laboratories; low molecular weight heparin; Molecular weight; Pathogenesis; Patients; Pharmacogenetics; Pharmacogenetics - methods; pharmacogenomics; Platelet factor 4; Platelet Function Tests - methods; Platelets; Polymorphism; Polymorphism, Single Nucleotide - genetics; Prevention; Risk Factors; Side effects; Special Report; Thrombocytopenia; Thrombocytopenia - chemically induced; Thrombocytopenia - genetics; Thromboembolism; Thrombosis; United States > US; heparin; genetics; pharmacogenomics; genome-wide association study; heparin-induced thrombocytopenia; low molecular weight heparin; anticoagulant; biomarker
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/pgs-2018-0147

Heparin-induced thrombocytopenia (HIT) is a life-threatening, immune-mediated adverse reaction to heparin anticoagulants. The inability to predict HIT represents a considerable liability associated with heparin administration. Genetic studies of HIT are challenging due to the scarcity of true HIT cases, potential for misclassification, and many environmental risk factors. Genetic studies have not consistently identified risk alleles for HIT, the production of platelet factor 4/heparin antibodies or the thromboembolic complications of HIT. Genes implicated in HIT and platelet factor 4/heparin antibody levels include and others. Compelling evidence also suggests that the H131R polymorphism is associated with HIT-related thrombosis. There is a need for well-powered, multiethnic studies with laboratory confirmation of HIT, detailed patient- and drug-specific data, and inclusion of both serologic and thromboembolic outcomes. Genomic biomarkers identified from such studies offer the possibility of shifting current clinical practice paradigms from early detection and treatment to prevention.